A study of the inclusion complex of bioactive thiadiazole derivative with 2‑hydroxypropyl‑β‑cyclodextrin: Preparation, characterization and physicochemical properties

Abstract

The main aim of this work has been to improve the solubility of bioactive 6-(acetylamino)-N-(5-ethyl-1,3,4-thiadiazol-2-yl)-hexanamide by forming an inclusion complex with 2-hydroxypropyl-β-cyclodextrin. UV–vis spectroscopy was applied to studying the host-guest interaction in the buffer solution pH 7.4. Phase solubility and Job's methods were used to confirm the formation of an inclusion complex with 1:1 stoichiometry and 103 kg·mol−1 stability constant. It has been established that in the presence of 0.069 mol·kg−1 of 2HP-β-CD, the compound solubility is equal to 11.60·10−3 mol·kg−1, which corresponds to a 7-time increase in this parameter compared to the solubility in pure buffer. The thermodynamic functions of complex formation have been determined and it has been found that the inclusion process is spontaneous and thermodynamically advantageous. Data from 1H NMR experiments also provided formation evidence of the inclusion complex between study compound and 2HP-β-CD. The inclusion complex in solid state has been obtained by grinding and characterized by differential scanning calorimetry, Fourier-transform infrared spectroscopy and X-ray diffractometry. The kinetic characteristics of dissolution process for the supramolecular complex have been obtained.